Arginine:glycine amidinotransferase deficiency

Description

Arginine:glycine amidinotransferase deficiency is an inherited disorder that primarily affects the brain. People with this disorder have mild to moderate intellectual disability and delayed speech development. Some affected individuals develop autistic behaviors that affect communication and social interaction. They may experience seizures, especially when they have a fever.

Children with arginine:glycine amidinotransferase deficiency may not gain weight and grow at the expected rate (failure to thrive), and have delayed development of motor skills such as sitting and walking. Affected individuals may also have weak muscle tone and tend to tire easily.

Frequency

The prevalence of arginine:glycine amidinotransferase deficiency is unknown. The disorder has been identified in only a few families.

Causes

Mutations in the GATM gene cause arginine:glycine amidinotransferase deficiency. The GATM gene provides instructions for making the enzyme arginine:glycine amidinotransferase. This enzyme participates in the two-step production (synthesis) of the compound creatine from the protein building blocks (amino acids) glycine, arginine, and methionine. Specifically, arginine:glycine amidinotransferase controls the first step of the process. In this step, a compound called guanidinoacetic acid is produced by transferring a cluster of nitrogen and hydrogen atoms called a guanidino group from arginine to glycine. Guanidinoacetic acid is converted to creatine in the second step of the process. Creatine is needed for the body to store and use energy properly.

GATM gene mutations impair the ability of the arginine:glycine amidinotransferase enzyme to participate in creatine synthesis, resulting in a shortage of creatine. The effects of arginine:glycine amidinotransferase deficiency are most severe in organs and tissues that require large amounts of energy, especially the brain.

Learn more about the gene associated with Arginine:glycine amidinotransferase deficiency

Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 1

• GATM

Inheritance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Other Names for This Condition

• AGAT deficiency • Cerebral creatine deficiency syndrome 3 • Creatine deficiency syndrome due to AGAT deficiency • GATM deficiency • L-arginine:glycine amidinotransferase deficiency • L-arginine:glycine aminidotransferase deficiency

Additional Information & Resources

Genetic Testing Information

• Genetic Testing Registry: Arginine:glycine amidinotransferase deficiency (https://ww w.ncbi.nlm.nih.gov/gtr/conditions/C2675179/)

Genetic and Rare Diseases Information Center

• L-arginine:glycine amidinotransferase deficiency (https://rarediseases.info.nih.gov/di seases/10323/l-arginineglycine-amidinotransferase-deficiency)

Patient Support and Advocacy Resources

• Disease InfoSearch (https://www.diseaseinfosearch.org/) • National Organization for Rare Disorders (NORD) (https://rarediseases.org/)

Research Studies from ClinicalTrials.gov

• ClinicalTrials.gov (https://clinicaltrials.gov/ct2/results?cond=%22arginine%3Aglycine +amidinotransferase+deficiency%22)

Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 2 Catalog of Genes and Diseases from OMIM

• CEREBRAL CREATINE DEFICIENCY SYNDROME 3 (https://omim.org/entry/6127 18)

Scientific Articles on PubMed

• PubMed (https://pubmed.ncbi.nlm.nih.gov/?term=%28arginine+glycine+amidinotran sferase+deficiency%29+AND+english%5Bla%5D+AND+human%5Bmh%5D+AND+ %22last+3240+days%22%5Bdp%5D)

References

• Braissant O, Henry H, Béard E, Uldry J. Creatine deficiency syndromes and the importance of creatine synthesis in the brain. Amino Acids. 2011May;40(5):1315-24. doi: 10.1007/s00726-011-0852-z. Epub 2011 Mar 10. Review. Citation on PubMed ( https://pubmed.ncbi.nlm.nih.gov/21390529) • Béard E, Braissant O. Synthesis and transport of creatine in the CNS:importance for cerebral functions. J Neurochem. 2010 Oct;115(2):297-313. doi:10.1111/j.1471- 4159.2010.06935.x. Epub 2010 Aug 25. Review. Citation on PubMed (https://pubme d.ncbi.nlm.nih.gov/20796169) • Comeaux MS, Wang J, Wang G, Kleppe S, Zhang VW, Schmitt ES, Craigen WJ, RenaudD, Sun Q, Wong LJ. Biochemical, molecular, and clinical diagnoses of patientswith cerebral creatine deficiency syndromes. Mol Genet Metab. 2013Jul;109( 3):260-8. doi: 10.1016/j.ymgme.2013.04.006. Epub 2013 Apr 17. Citation on PubMed (https://pubmed.ncbi.nlm.nih.gov/23660394) • Edvardson S, Korman SH, Livne A, Shaag A, Saada A, Nalbandian R,Allouche- Arnon H, Gomori JM, Katz-Brull R. l-arginine:glycine amidinotransferase (AGAT) deficiency: clinical presentation and response to treatment in twopatients with a novel mutation. Mol Genet Metab. 2010 Oct-Nov;101(2-3):228-32.doi: 10.1016/j. ymgme.2010.06.021. Epub 2010 Jul 7. Citation on PubMed (https://pubmed.ncbi.nlm .nih.gov/20682460) • Item CB, Stöckler-Ipsiroglu S, Stromberger C, Mühl A, Alessandrì MG, BianchiMC, Tosetti M, Fornai F, Cioni G. Arginine:glycine amidinotransferase deficiency:the third inborn error of creatine metabolism in humans. Am J Hum Genet. 2001Nov;69(5): 1127-33. Epub 2001 Sep 10. Citation on PubMed (https://pubmed.ncbi.nlm.nih.gov/1 1555793) or Free article on PubMed Central (https://www.ncbi.nlm.nih.gov/pmc/articl es/PMC1274356/) • Nasrallah F, Feki M, Kaabachi N. Creatine and creatine deficiency syndromes: biochemical and clinical aspects. Pediatr Neurol. 2010 Mar;42(3):163-71. doi:10. 1016/j.pediatrneurol.2009.07.015. Review. Citation on PubMed (https://pubmed.ncbi. nlm.nih.gov/20159424) • Schulze A. Creatine deficiency syndromes. Mol Cell Biochem. 2003Feb;244(1-2): 143-50. Review. Citation on PubMed (https://pubmed.ncbi.nlm.nih.gov/12701824)

Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 3 • Stromberger C, Bodamer OA, Stöckler-Ipsiroglu S. Clinical characteristics and diagnostic clues in inborn errors of creatine metabolism. J Inherit Metab Dis.2003;26( 2-3):299-308. Review. Citation on PubMed (https://pubmed.ncbi.nlm.nih.gov/128896 68) • Sykut-Cegielska J, Gradowska W, Mercimek-Mahmutoglu S, Stöckler-Ipsiroglu S. Biochemical and clinical characteristics of creatine deficiency syndromes. ActaBiochim Pol. 2004;51(4):875-82. Review. Citation on PubMed (https://pubmed.n cbi.nlm.nih.gov/15625559) • Verma A. Arginine:glycine amidinotransferase deficiency: a treatable metabolicencephalomyopathy. Neurology. 2010 Jul 13;75(2):186-8. doi:10.1212/ WNL.0b013e3181e7cabd. Citation on PubMed (https://pubmed.ncbi.nlm.nih.gov/206 25172)

Page last updated on 19 April 2021

Page last reviewed: 1 December 2015

Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 4